Bioerodible self-deployable intragastric implants and methods for use thereof

ABSTRACT

Described herein are bioerodible, biodegradable, or digestible self-deploying intragastric implants that may be swallowed. Once swallowed, the implants undergo self-expansion in the stomach and apply a suitable pressure against the stomach wall to provide a feeling of satiety to the individual. The implants then dissolve or are disassembled perhaps using gastric liquids and pass out of the stomach. Methods of using the devices, perhaps for an individual participating in a dietary control regimen, are described.

RELATED APPLICATIONS

This application is a continuation of U.S. Ser. No. 11/788,574, now U.S.Pat. No. 7,785,291, which is a continuation-in-part of U.S. Ser. No.11/519,508, filed Sep. 11, 2006 (now U.S. Pat. No. 7,699,863), which isa continuation-in-part of International Application No.PCT/IL2006/000276, filed Mar. 1, 2006, claiming priority from IsraeliApplication No. 167,194, filed Mar. 1, 2005, and which U.S. applicationfurther claims priority under 35 USC 119(a) from Israeli Application No.176,856, filed Jul. 13, 2006. The entirety of each of these documents isincorporated by reference for all reasons.

FIELD

Described herein are bioerodible, biodegradable, or digestibleself-deploying intragastric implants that may be swallowed. Onceswallowed, the implants undergo self-expansion in the stomach and applya suitable pressure against the stomach wall to provide a feeling ofsatiety to the individual. The internal components that provide gas forexpansion of the implant may be deployed by mechanical mixing, fractureof an frangible component, manual manipulation, or the like. Theimplants then dissolve or are disassembled perhaps using gastric liquidsand pass out of the stomach. Methods of using the devices, perhaps foran individual participating in a dietary control regimen, are described.

BACKGROUND

Obesity is a major health problem in developed countries. In the UnitedStates, the complications of obesity affect nearly one in fiveindividuals at an annual cost of approximately $40 billion. Except forrare pathological conditions, weight gain is often directly correlatedto overeating.

One strategy for controlling the individual's food intake is via the useof intragastric volume-occupying devices. Such devices are placed in thestomach and occupy a portion of its interior. Properly placed and sized,the intragastric volumes provide the patient with a feeling of satietyafter having eaten only a smaller amount of food. Typically, theindividual's caloric intake is thus diminished due to the subjectivefeeling of fullness. There are a number of available volume-occupyingdevices. Many must be introduced using surgical or other complex gastricprocedures.

Intragastric balloons have been in clinical use for several years. Theirsuccess in the treatment of certain individuals with morbid obesity iswell accepted.

Published U.S. Patent Application No. 2004/0186502, U.S. Pat. No.6,981,980, and published PCT application WO/2006/020929, to Sampson etal, each disclose inflatable, intragastric volume-occupying balloonsincluding a valve that provides fluid communication into the balloonfrom outside the body. The '502 application further discloses a methodfor occupying some amount of stomach volume comprising the step ofinserting the deflated balloon into the stomach through the esophagus,inflating the balloon by introducing an activating liquid through theself-sealing valve. Each document describes selection of polymersallowing gastric erosion of the balloon and causing its subsequentdeflation.

Published PCT Application WO/2006/044640, to Baker et al, shows animplant used as a bariatric device situated along certain walls of thestomach to induce a feeling of satiation.

Published U.S. Patent Application 2004/0192582, to Burnett et al, showsa composition and a device that expands in the stomach after swallowingand provide a temporary, erodible volume and consequent diminution ofgastric volume in the stomach.

U.S. Pat. Nos. 6,271,278 and 5,750,585, each to Park et al, showcompositions of swellable, superabsorbant-hydrogel composites that maybe used in gastric retention treatments for obesity.

U.S. Pat. No. 4,607,618, to Angelchik, discloses an intragastric devicemade up of semi-rigid skeleton members, collapsible to a shape, andhaving dimensions suitable for endoscopic insertion into the stomachthrough the esophagus.

U.S. Pat. No. 5,129,915, to Cantenys, relates to an intragastric balloonthat is intended to be swallowed and that inflates automatically underthe effect of temperature. The Cantenys patent lists three ways that anintragastric balloon might be inflated by a change in temperature.First, a composition of a solid acid and of a non-toxic carbonate orbicarbonate is temporarily kept from the fluid in the stomach by acoating of chocolate, cocoa paste, or cocoa butter. The chocolatecoating is selected to melt at body temperature. Secondly, a citric acidand alkaline bicarbonate composition coated a coating of non-toxicvegetable or animal fat melting at body temperature may be used. When inthe presence of water, the composition is said to produce the sameresult as does the earlier-discussed composition. Third, the solid acidand non-toxic carbonate or bicarbonate composition may be temporarilyisolated from water by an isolation pouch of a low-strength syntheticmaterial which is to break immediately upon swallowing. Breaking theisolation pouches causes the acid, carbonate or bicarbonate, and waterto mix and to react, thereby inflating the balloon. The balloon itselfis said to be made up of a modestly porous, but non-digestible materialthat allows slow deflation.

WO/2005/039458 shows a gastric constriction device that is to be mountedexterior to the stomach and cause feelings of satiation due to pressureon the vigil nerves of the stomach.

WO/2005/101983, to Dharmadhikari, shows an expandable composition thatmay be used as a gastric retention system, with or without the presenceof ancillary drugs.

U.S. Pat. No. 5,783,212, to Fasihi et al, shows an expandable, erodiblepolymeric composition that may be used in drug delivery systems.

U.S. Pat. No. 6,733,512, to McGhan, describes an intragastric balloonhaving erodible patches that allow self-deflation of the balloon after achosen period of residence in the stomach.

None of the cited documents discloses the bioerodible intragastricimplant deliverable to the stomach by conventional oral administrationthat is described below.

SUMMARY

Described herein are devices for and related methods for curbingappetite and for treating obesity. These treatments may be used inproviding selective medical care and obesity therapy and arespecifically suited to treatment of an individual patient while takinginto account an individual's eating habits; differences in theindividual's daytime and nighttime behavior; physiological and mentalcharacteristics, body size, and age.

The devices include cost effective, biodegradable, self-inflatingintragastric implants for curbing appetite and treating obesity,constructed from one or more discrete expandable members that areerodible in the stomach.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 shows a perspective view of one variation of structural framemembers suitable for use in this implant.

FIGS. 2A and 2B show, respectively, a perspective view and an end viewof one variation of an implant comprising a structural frame member.FIGS. 2C and 2D show isolated sections of the FIGS. 2A and 2B implant.

FIGS. 3-11 show perspective views of several variations of structuralframe members suitable for use in this implant.

FIGS. 12A and 12B show, respectively, a side view and an endcross-section view of one variation of a folded implant comprising astructural frame member.

FIG. 13 shows a side view of one variation of a folded implantcomprising a structural frame member, panels, and stabilizer members.

FIG. 14 shows perspective views of a folded and expanded implantcomprising a structural frame member and panels.

FIGS. 15A-15F show various panel structures.

FIG. 16 shows a perspective view of a variation of an implant comprisinga structural frame member and panels.

FIG. 17 shows a top view of an unfolded implant comprising a structuralframe member and panels.

FIG. 18 shows a perspective view of an expanded implant comprising astructural frame member and panels.

FIG. 19 shows a top view of an unfolded implant comprising a structuralframe member and panels.

FIGS. 20A, 20B, and 20C show, respectively, a perspective view of adeployed implant, a top view, and a perspective view of a folded implantcomprising a structural frame member and panels.

FIG. 21 shows a top view of an unfolded circular implant comprising astructural frame member and a panel.

FIGS. 22-24 show perspective views of several versions of unfoldedimplants each comprising a structural frame member and panels.

FIGS. 25A and 25B show, respectively, a top view and a perspective viewof an unfolded coil-like implant comprising a structural frame memberand panels.

FIGS. 26A-26C show, respectively, a perspective and two side views ofsubstantively globe-like implants.

FIGS. 27A and 27B show, respectively, a perspective view and a sidecross-sectional view of two related self-inflating implants.

FIG. 28 is a perspective view of a variation of the implant in anuninflated configuration.

FIG. 29 is a top view of the implant variation shown in FIG. 28 afterinflation or expansion.

FIG. 30 is a schematic representation of an appropriate placement of ourimplant within the stomach.

FIG. 31 is a perspective view of another variation of our implant.

FIG. 32 is a perspective view of a variation of our implant.

FIGS. 33A to 33C-1 provides perspective views of a several inflatedvariations of our implant.

FIG. 33C-2 is a cross-section of the implant shown in FIG. 33C-1.

FIGS. 33D to 33E provide perspective views of two inflated variations ofour implant.

FIG. 34A is a partial cross section of an expanded implant showing anexpanded hoop portion and a container, at least partially contained inthe hoop, containing a composition that produced an expanding gas.

FIG. 34B is a perspective view of the container containing the expandinggas composition.

FIG. 35 shows the production of an implant that may be swallowed and theseparation of the gas-producing composition components untilappropriately mixed.

FIGS. 36-38 show side cross-sectional views of variations of valvemembers controllable in mixing components of the gas-producingcomposition.

FIG. 39 shows a side cross-sectional view of a folded member forcontrolling the isolation of components of the gas-producingcomposition.

FIGS. 40A-40C show side cross-section views of frangible gas-producingcomponents with fracturable outer shells, enclosing a singlegas-producing chemical.

FIGS. 41A-41C show side cross-section views of frangible gas-producingcomponents with various walls that are fracturable, enclosing twogas-producing chemicals.

FIG. 42 shows a side cross-section view of a frangible gas-producingcomponent with a single fracturable outer shell, enclosing a singlegas-producing chemical, and positioned against and using a wall of theexpandable implant as a barrier.

FIG. 43 shows before-and-after, side cross-section views of a frangiblegas-producing component with at least one interior, fracturable wall,enclosing two gas-producing chemicals, that causes consequentialfracture of other component walls upon reaction of an initiator amountof one of the gas-producing chemicals.

FIG. 44 shows before-and-after, side cross-section views of a frangiblegas-producing component illustrating a fracture that opens a passagewaybetween chambers enclosing two reactive gas-producing chemicals.

FIG. 45 shows a close-up, side-view, cross-section of the fracturedopening shown in FIG. 44.

FIG. 46 shows a side-view, cross-section of a pair of non-fracturableenclosures for the two reactive gas-producing chemicals separated by afracturable joint of the type shown in FIGS. 44 and 45 and employing theouter implant wall as a barrier for the enclosures.

DESCRIPTION

Described herein are bioerodible intragastric implants that are usefulin curbing appetite and that are constructed from one or more discreteexpandable members. The implants may be swallowed and may beself-deployable. Also described are treatments for curbing anindividual's appetite by using those devices.

The device curbs the appetite by temporarily expanding within thestomach to form a structure that contacts some portion of the stomachwall. When the implant is self-deploying, it expands in the stomach bybeing filled with a gas from a source that is swallowed with the deviceenvelope or bladder. The described devices may be configured then todissolve or to degrade after a selected period of time and be eliminatedfrom the stomach.

The described self-deploying implant may be deployed in the stomachusing, e.g., members comprising materials having “shape memory”characteristics or having significant elastic properties (e.g.,elasticity or superelasticity of metals, alloys, or polymers) or otherflexible constituent materials otherwise adapted to expand the devicewhen placed in the stomach. The compositions are at least biocompatibleand are desirably themselves bioerodible.

The device may comprise a single expandable member that expands uponintroduction into the stomach or may comprise a plurality of discreteexpandable members with attachments to other members or to a framework.Some variations of the device involve expansion of the member or membersvia use of an included amount of a carbon dioxide generating composition(CDGC).

Typically, the discrete expandable member of the type that isinterconnected to another member is of one or more variations. In thefirst variation, the expandable member may be of a size and material,etc., that upon destruction of the connection to other members, it maybe eliminated from the stomach without need for additional dissolution.In the other variation, the member is of a size and material in whichfurther bioerosion is appropriate before the resultant member debriseasily evacuates from the stomach.

As noted above, the various described members are desirably expandablein vivo upon contact with gastric juice. That expansion may take placeover a predetermined and, perhaps extensive, period of time. The periodof time during which the members erode to a size and form that passesfrom the stomach is similarly variable depending upon the resultdesired.

Expansion and dissolution times may each vary from about 0.25 hour to asmuch as 30 days. Obviously, the expansion times should be chosen toallow the stomach to activate the self-deploying feature of our devicesbefore the stomach attempts to eliminate the device without deploymentto the detriment of the stomach and the device.

Such predetermined time periods are to be selected by the medicalspecialist and reflect inter alia the size of the stomach, the age ofthe patient, the physical condition of the patient, food digestiveparameters in the stomach and along the digestive tract, the medicalcondition of the stomach and its sphincters, the content of the gastricjuice, and the patient's general physiological and mental condition.

The described devices are self-inflating or self-expanding and do notinclude external inflating valving for inflation of the implant fromexternal sources after the implant has been deployed.

DEFINITIONS

By the term “discrete expandable member,” we mean that a specific memberor component is itself expandable and may be temporarily interconnectedto at least one other member, perhaps a structural element or perhaps asa portion of a structural element, by a bioerodible component, e.g., atie.

By the term “bioerodible” we mean that the material is biodegradable,digestible, or erodible or otherwise dissolvable or degradable in thestomach to a form where the material is diminished in size by chemical,biological (e.g., enzymatic), physical dissolution, solubilization, etc.to allow elimination of the material from the stomach withoutsubstantial harm.

By the term “self-inflating” we refer to a spontaneous self-inflationfeature. The implant need not include any inflating valves or the like,nor external inflating means.

By the term “pasta” we refer to mixtures of carbohydrates, e.g., flourand fluids, e.g., water, possibly with a predetermined measure ofproteins, especially egg-related proteins.

By the term “gelatin” we refer to a protein product derived throughpartial hydrolysis of the collagen extracted from skin, bones,cartilage, ligaments, etc.

By the term “about” we refer to a tolerance of ±20% of the definedmeasure.

Frame and Panel Structures

FIG. 1 shows a flexible biodegradable structural member (100) comprisinga number of hollow tubular members (102) having passageways (104)therethrough and joined by a thread, cord, or wire (106). The thread,cord, or wire (106) may have characteristics of high elasticity,super-elasticity, or temperature shape memory allowing it to return toor form a desired shape upon being placed in the environment of thestomach. For instance, the structural member (100) may include a thread,cord, or wire (106) that includes shape memory characteristics allowingit to be compressed/twisted/folded or otherwise deformed into a smallvolume for introduction into the comparatively elevated temperature ofthe stomach and to re-form into a desired shape suitable for pressingonto the sidewalls of the stomach. The thread, cord, or wire (106) maycomprise a bioerodible material or another material, as desired.

Expandable tubular members (102) may comprise a material that isexpandable upon introduction into the stomach and is bioerodible to aform and size that may be eliminated from the stomach. Such materialsare discussed elsewhere in a section specifically discussing thosematerials.

FIGS. 2A and 2B show an expanded framework (110) comprising a generallyovoid, football-shaped framework constructed from a number of structuralmembers (100) or other similar structural members such as are discussedwith relation to several of the following Figures.

FIG. 2A shows a perspective view of the expanded framework (110) wherethe structural members (100) are joined at a number of locations (112)to form the desired shape. Other expanded shapes may also be apparent tothe knowledgeable designer, e.g., stomach shaped, cup-shaped, etc. Inany event, the end sections (114) comprise rounded triangular areas (115also shown in isolation in FIG. 2C)—the edges being defined by thestructural members (100). Triangles are two-dimensional structural formsthat are sturdy and support the form of the structure. In the inner twosections (116), the four-sided areas (117 also shown in isolation inFIG. 2D) may be strengthened by exterior struts (118) and interiorstruts (120) if so desired or needed.

The expanded form (110) shown in FIGS. 2A and 2B may be used as shown ormay be used as a framework for supporting panels or the like as will bediscussed below.

FIGS. 3-12 show other variations of structural members of suitable foruse in the same way as is the structural member (100) shown in FIGS. 2Aand 2B.

FIG. 3 shows a structural member (120) comprising a series of cylinders(122) secured to each other by ties comprising an elastomeric or rubberymaterial (124). As with the variation discussed with regard to FIGS. 2Aand 2B, structural member (120) and the ties (124) may comprise amaterial that is expandable upon introduction into the stomach and isbioerodible to a form and size that may be eliminated from the stomach.

FIG. 4 shows another structural member variation (126) comprising aseries of erodible expandable tubular members (128) having a thread,cord, or wire (130) extending throughout. The variation (126) alsocomprises several strengthening biodegradable wires (130) attached tothe tubes (128) at the joints.

FIG. 5 illustrates another variation of the structural member (132)having strengthening biodegradable wires (130) but without the thread,cord, or wire or securing material included in the variations shown inFIGS. 1, 3, and 4.

FIG. 6 shows a variation of the structural member (136) having erodibleexpandable tubular members (128) but, unlike the other variations, has acoiled center member (138) linking the erodible expandable members(128). The coiled center member (138) may comprise a bioerodiblematerial possibly having characteristics of high elasticity,super-elasticity, or temperature shape memory allowing it to return toor to form a desired shape upon being placed in the environment of thestomach.

FIG. 7 illustrates a similar variation (140) wherein the structuralframework comprises a spring-like member (142) comprising one or morebiodegradable materials.

FIG. 8 shows a variation (146) of the structural frame member comprisinga hollow flexible biodegradable tube (148) full of gas. The tube (148)is filled with a gas upon introduction into the stomach using aself-contained gas source such as is discussed below.

FIG. 9 shows a further variation of the framework (150) having multiplespring-like members (152) interconnected using ties (154) along itslongitudinal axis. The ties (154) may comprise an elastomeric or rubberymaterial. As discussed elsewhere, the ties (154) may comprise a materialthat is expandable upon introduction into the stomach and that isbioerodible to a form and size that may be eliminated from the stomach.

FIG. 10 shows a further variation of the framework (160) having sections(161) each comprising dual, substantially parallel elastic wires (162)separated by pinch-point joints (163). Again, the wires may comprise abioerodible material. This framework variation (160) is able to becompressed or folded and to return to a desired shape upon release intothe stomach.

FIG. 11 shows still a further variation (164) of the framework in FIG.10 with sections, each section comprising dual, substantially parallelelastic wires (166) but having joints or flexible ties (168) joining thesections of wires. The ties (168) are of a material different than thewires (166).

As we discussed above, the structural frameworks shown above may be usedin isolation as shown generally in FIGS. 2A and 2B. They may also beused as a support or structural frame for sheets or for inflatableenvelopes or gastric balloons, as is discussed below. In any event, ifthe framework is used in isolation to provide pressure on the stomachwall, such a framework would be compressed, twisted, folded, orotherwise compacted or reduced to a form that may be swallowed by apatient.

The structural framework may also be characterized as ribs having ends,e.g., proximal and distal ends. Such ends may comprise sliding ends, inthat they may be connected to other structural members in such a waythat they slide with respect to that other member. For instance, thesliding ends may be forked or circular, with the other member situatedwithin the open end of the fork or within the opening of the circularend. Such sliding ends may further comprise rotating hinges or aprotruding element that cooperates with a slot or similar opening in theother element allowing a siding movement along the axis of that othermember. Each of these ends may be used, dependent upon the design of thespecific structure employed, to facilitate expansion or deployment ofthe implant structure in the stomach.

In some instances, the compacted form—the form of the device before itis deployed in the stomach—may be in a self-contained tension andrequire one or more components, denominated “shape stabilizers” tomaintain that tension and to hold the compacted form in a swallowableform until reaching the stomach. The shape stabilizers may be made frommaterials that are bioerodible and desirably are of a form or shape thaterode (and release) initially after being introduced into the stomachand therefore allow self-deployment.

FIG. 12A shows a generic representation of an implant assembly (169)that has been folded and compressed into a swallowable shape and sizewith a framework or set of structural members (171) and having a numberof shape stabilizers (173) comprising a biodegradable material, e.g.,gelatin or polyglycolide, that has been applied about the framework(171) to maintain it in a compressed condition until the stabilizer orstabilizers have eroded to allow self-implantation. Such shapestabilizers may be of a variety of forms, e.g., strings, ribbons,capsules, dried hydrogels (perhaps of gelatin or polyglycolide or thelike) and other bioerodible forms.

FIG. 12B shows a cross-section of the FIG. 12A device showing, inparticular, the structure of the stabilizing shape stabilizer (173)about the framework members (171).

FIG. 13 shows another folded device using shape stabilizers.Specifically, FIG. 13 shows a folded framework (170) having a number ofstructural members (172) folded at ties (174) into a swallowable packageand secured into that package by a bioerodible string or twine (176)that is looped about the package. The securing twine or string shapestabilizer (176) may optionally be tied using a “running” knot or “sack”knot. The securing twine or string (176) may be bioerodible to allowself-expansion of the folded framework (170).

FIG. 14 shows a generic representation of the construction of an implant(180(a) folded and ready for placement in the stomach) and that implant(180(b)) after self-deployment in the stomach. The depiction of theimplant after deployment (180(b)) shows several structuralmembers—circumferential structural members (182) and longitudinalstructural members (184). Those members are connected to panels (186).Other variations of these generic structures are discussed elsewhere.

FIGS. 15A to 15F show representative cross-sections of materials thatmay be used in the panels or sheets mentioned elsewhere. The panels orsheets may be constructed in such a way that they are bioerodible in thestomach, bioerodible after passing through the stomach, or notbioerodible. The sheets or panels may be constructed in such a way thatthey have selectively erodible pathways that allow the structure tomaintain its effective shape in the stomach and then to degenerate intosmaller portions that may be further eroded either in the stomach orafter passing out of the stomach.

FIG. 15A shows a portion of a panel (190) comprised of a bioerodiblematerial (192) that generally is to be substantially eroded in thestomach. FIG. 15B shows a portion of a panel (194) comprised of abioerodible material (192) that generally is to be substantially erodedin the stomach. A number of grooves (196) are included. The grooves(196) allow the panel (194) to be eroded in the stomach into smallersections, e.g., section (198), that are non-structural in nature and maybe eroded in the stomach. The grooves allow step-wise removal of thedescribed implant from the stomach in a controlled manner.

FIG. 15C shows another panel (200) made up of a layer (202) comprised ofa comparatively more erodible material, perhaps of the same class ofmaterials used in layer (192) in FIG. 15A, and a layer (204) of amaterial that is in the class generally used as “enteric coatings.” Theenteric coating layer (204) is shown in the Figure as being on only oneside; such a layer may be placed on both sides of the panel, though.

FIG. 15D shows another representative panel (206) also having a layer(208) comprised of a comparatively more erodible material, again perhapsof the same class of materials used in layer (192) in FIG. 15A, and anenteric material layer (210) having grooves (212) or other openings inthe enteric coating into the more erodible material layer (208). Thegrooves (212) allow the panel (206) to be eroded in the stomach intosmaller sections, e.g., section (211), that are non-structural in natureand may be eroded either in the stomach or after passage from thestomach. These grooves (212) also allow step-wise removal of thedescribed implant from the stomach in a controlled manner. Again, theenteric coating layer (210) is shown in FIG. 15D as being on only oneside, such a layer may be placed on both sides of the panel (206) withor without the depicted grooves.

FIG. 15E shows a representative panel (213) comprising filamentarycomponents (215) stuck together to form an open weave materialcomprising one or more biodegradable materials. Such fabrics may bewoven or nonwoven fabrics of filamentary materials as well.

FIG. 15F shows another representative panel (217) comprising a sheetmaterial having protrusions (219).

In general, the panels may comprise membranes or sheets, fabrics ofassembled filaments (onlays, woven, or non-woven), meshes, screens,knits, etc. The panels may be stiff or very pliable. They may be layeredconstructs or neat materials. They may have physical properties allowingthe expanded implant to provide pressure upon the stomach wall. They maybe so highly flexible that they are easily twisted or compressed intosmall compact packages.

Materials suitable as “enteric coatings” are provided in a separatesection herein.

FIG. 16 shows a form of an implant (210) that is cup-like in shape. Theform comprises four panels (212) and a bottom (214, not visible in FIG.16). The depicted form may be considered as a schematic starting form inthat it may be further compressed or folded. The panels (212) may bemade of the compositions discussed above.

FIG. 17 shows a flattened form of the implant (210) shown in FIG. 16with the side panels (212) and bottom (214). Structural members (218)around the edges of the panels (212) and a structural member (220)around the edge of the bottom panel (214) are also shown.

FIG. 18 depicts a conical implant (230) as-deployed, with acircumferential support structure member (232) and a radial supportmember (234). The supported panel (236) is also shown.

FIG. 19 also shows the implant (230) in the pre-formed shape having thecircumferential support structure member (232), radial support member(234), and supported panel (236). The support members (232, 234) may beintegrated into the panel (236) or linked to the panel (236) via tiemembers that may either comprise bioerodible materials or otherbiocompatible materials.

The conical deployed form shown in FIGS. 18 and 19 is an elected form.That is to say: the material making up the panel (236) may be “open” inthe sense that it may be an “open weave” fiber material allowing fluidand solid flow through the field of the panel. The conical form allowsdeployment of the implant (230) in such a way that the circumferentialstructural member (232) rests against the stomach wall and impartspressure against that wall providing a feeling of satiation. The“upstream” pressure of the liquids and solids inside the implantprovides a continuing pressure against the circumferential structuralmember (232) until that member erodes sufficiently to pass from thestomach.

The radial structural member (234) provides a measure of directionalityto the placement of the implant (230) in the instance where theconnecting joint (238) provides some measure of rigidity to the unfoldedstructure of the implant (230). If radial member (234) is sufficientlylong, e.g., longer than the diameter of the stomach and the connectingjoint (238) is rigid (i.e., the joint sets the angle of the radialmember (234) with respect to the circumferential member (232) as shownin FIG. 18) or allows the radial member (234) only a small amount ofrotation with respect to the circumferential member (232), the radialmember (234) acts as a “director” and tends to align the circumferentialmember (232) across the stomach and to press the member (232) againstthe stomach wall.

As a design choice, the radial member (234) may be omitted so to allowthe flow resistance of the panel (236) to align the circumferentialmember against the stomach wall, albeit with a slower alignment ratethan with a device having the radial member.

FIGS. 20A, 20B, and 20C show a truncated conical implant (240) having asmaller opening (242) and a larger opening (244). The implant (240) alsoincludes a panel (245), larger circumferential support member (246),smaller circumferential support member (248), and longitudinal supportmember (250). The truncated cone shape permits passage of stomachcontents through the stomach without substantial interference and yetstill utilizes that flow to align the implant in the stomach, in thatthe modest flow resistance tends to push the large end against thestomach wall.

FIG. 20C shows a collapsed implant (240) of the type shown in FIGS. 20Aand 20B with a shape stabilizer (241) ready for introduction into apatient.

FIG. 21 shows a circular implant (260) having a panel (262) and anexterior circumferential support structure (264). The circumferentialsupport structure (264) comprises, in this variation, a series ofsegments (266) joined by ties (268) as discussed above with respect toFIGS. 1 and 3-5. In this instance, the panel (262) may be perforated,with one or more openings through the panel. Such a panel includes thefurther advantage of slowing movement through the stomach in addition tothe benefit of pressing upon the stomach wall.

Central to the use and configuration of our implant is the concept thatthe implant size and configuration be appropriate and sufficient toprovide a pressure on the stomach wall to initiate and to continue thatpressure prior to its shape degradation and passage from the stomach.Several suitable expanded implant shapes are discussed above with regardto FIGS. 2A, 2B, 14, 16, 18, and 20A.

Other suitable expanded implant forms particularly useful in frameworkand panel constructions are shown in FIGS. 22-26C. Still other suitableforms are discussed below.

FIG. 22 shows an expanded implant form (270) having a generallyhalf-football form comprising longitudinal structural members (272),partially circumferential structural members (274), and several panels(276). The partially circumferential structural members (274) generallyprovide pressure to the stomach wall.

FIG. 23 shows an expanded implant form (278) having a football-like formcomprising longitudinal structural members (280), a generally centralcircumferential structural member (282) that may be made up of severalpartially circumferential members, and several panels (284). In thisvariation, the circumferential structural members (282) may beconfigured to provide pressure to the stomach wall although the variouspanel (284) sizes and expanded stiffnesses may be chosen to form astructure that will provide pressure on the wall.

FIG. 24 shows a truncated football expanded implant form (290) similarin overall form to the variation shown in FIG. 22 with the generalexception that the small end has an opening (292) potentially with acircumferential structural member (294).

FIGS. 25A and 25B show a spiral configuration (298) of our implantcomprising a biased, structural member (300) of a spinal form that tendsto open when in a relaxed condition. The configuration may include oneor more smaller, circular, stiffening members (302). The structuralmember (300) may be considered to be a spring in compression, whendeployed, and is held in the depicted, stressed form by halter filament(304). The implant is shown with a columnar panel (306) that is twistedinto a spiral. Another structural member (not shown) may also beemployed, e.g., on the inner circumference of the spiral column andattached to the circular members, to provide additional structure to theimplant.

FIGS. 26A-26C show a variation of our implant (310) including astructural member that is springy (312) and that is easily twisted intosmaller circular forms for introduction into the stomach. The implant(310) is shown with a generic panel (314), in perspective view, to allowoverall understanding of the simplicity of the construction. FIG. 26Bshows the implant with a flexible sheet for the panel (316 a). FIG. 26Cshows the implant with comparatively stiffer sheets for the panel (316b).

The framework system discussed above is suitable for expanding, or toaid in supporting, variously the sheet structures specifically listedabove as well as self-expanding envelope structures exemplified above.

Self-Inflatable Structures Having Integral Gas Inflation Sources

Another variation of our implant comprises an efficient, self-inflating,or self-expanding implant that temporarily self-expands within thestomach of a patient using an integral gas source. Generally, when thisvariation of our implant is properly designed and sized, it willself-expand to a shape or to a diameter where the implant's perimeter isat least partially in contact with the interior surface of the stomachwall and thereby exerts at least a pressure on that portion of thestomach wall sufficient to trigger “fullness” responses from thestomach's nervous system. Functionally, the implant is sized to producesuch a feeling in a particular patient variously before or after apatient has eaten.

After the implant has been in place in the stomach for a predeterminedperiod of time, the implant will bioerode and pass through the stomachafter being partially or completely digested. To accomplish this goal,the implant may be made from one or more bioerodible materials such asthose listed herein, perhaps in combination with one or more entericmaterials, again, such as those listed herein.

The expanded implant may comprise, although it need not necessarily beso, a structure having a comparatively larger size in two dimensions anda smaller size in the third direction.

When properly designed, this variation of the implant will provide afeeling of satiety, with the goals of not producing an uncomfortablefeeling of fullness and without substantially changing conditions in thestomach, conditions such as temperature, digestive movements, pH, wateractivity (a_(w)), water availability in the stomach, and biologicalconditions such as the availability of digestive enzymes.

The implant self-expands due to the presence of an integral gas source.The gas source is “integral” in the sense that the components thatproduce the gas by chemical reaction, or biological process, or thelike, are within the swallowed envelope or are in fluid communicationwith the envelope that forms the exterior of the expanded implant.Further, the term “integral” means that the implant's expanding gas isthe product of a chemical or biological process based on gas-producingmaterials swallowed with the implant. The gas is neither added norsupplemented by a physical connection through a stomach opening. Theintegral gas source does not utilize gastric fluids as reactants in thegas source nor does the design of the implant permit the entry ofgastric fluids into the interior of the un-inflated implant. Externalmanipulation, e.g., via manual pressure or the like, may be used toinitiate operation of the integral gas source in some variations, butsuch manipulation does not include use of any tool or means that isphysically introduced into the stomach via the esophagus or via surgery.Such manipulation may, however, include the use of magnets or of appliedradio-frequency energy or of physical manipulation of the swallowedimplant via pressing with the hand or fingers to initiate, enhance, orcontinue the gas production process.

Although the gas source may, in a general sense, produce any gas thatwill inflate or expand the implant bladder or envelope, from a practicaland safety point of view, a very good choice for such an expansion gasis carbon dioxide. The solid or liquid components suitable (and readilyavailable) for producing carbon dioxide gas may be readily selected frommaterials that are themselves safe for human consumption. For instance,a suitable carbon dioxide source may comprise physically separatedamounts of bicarbonate of soda and of a vinegar solution. These twomaterials are safe for human consumption, have no reaction products thatare harmful, and are quite effective in producing carbon dioxide gas inamounts and at pressures that are useful in our implant. Only relativelysmall amounts of the reactants are needed to inflate the implantvariation.

Chemical reactants involving simple acid-base reactions to producecarbon dioxide that are especially suitable for the gas source include:basic materials such as sodium bicarbonate (NaHCO₃), sodium carbonate(Na₂CO₃), calcium bicarbonate (Ca(HCO₃)₃), calcium carbonate (CaCO₃),and the like. Suitable acidic materials include various organic acidssuch as those found in vinegar (acetic acid), citrus juices (lime,lemon, orange, grapefruit juices containing citric acid), Vitamin C(ascorbic acid), tartaric acid, etc. Other organic acids, especiallycarboxylic acids are also useful. Carbonic acid is also operable but is,as a practical matter, too unstable at room temperatures to be a firstchoice for the gas source.

As to the structure of this variation of our implant, FIG. 27A shows aperspective view of a flat-sided variation (320) comprising opposing,generally flat surfaces (322), an opening or passageway (324) throughthe implant to allow passage of stomach contents past the implant, andan outer periphery (325). The variation shown in FIG. 27A also includesa stub or extension (326) that may include one or more components of thegas source.

FIG. 27A also shows the conventions we use in describing the variousdimensions of this variation of the implant (320). The dimension “H” isthe diameter of the device. The dimension “T” is the thickness of thedevice and the dimension “D” is the difference between “H” and thediameter of the inner opening (324).

The depiction of the implant (320) shown in FIG. 27A depicts an outerperiphery (325) having a relatively right-angled shoulder or edge. FIG.27B shows a cross-section of another implant variation (330) in whichthe expanded form has opposing surfaces (332), an outer generallyrounded periphery (334), and a rounded inner surface (336), surroundinga central opening or passageway (338). This variation (330) may bereferred to as having a toroidal or donut shape.

In general, these variations of our implant, when expanded, comprise aconfiguration that has a generally flat shape in which D<H and T<H, theexternal periphery (325, 334) of which is selected to press against thesidewalls of the stomach. Typically, the “H” dimension of the expandedor inflated envelope is functionally in the range of about 75% to about110% of the inner latitudinal diameter of the stomach, typically lessthan about 15 cm. The pre-inflated envelope or bladder (but not yetrolled or otherwise folded into the swallowable form) may have “T” and“D” dimensions of less, even substantially less, than about 2 cm.

The functional and physical sizes mentioned here with respect to theself-inflating implant variations of the device are, of course, basedupon the implant's relationship with the size of the stomach. Thesesizes are also suitable for the frame-based variations discussed above.

The dimensions of such a partially or fully expanded implant may vary,e.g., the “D” dimension may be between about 0.2 and about 3.0 cm,perhaps between about 1.2 and about 1.8 cm, and perhaps between about0.75 and about 1.5 cm; the “H” dimension typically will be between about8 and about 18 cm, perhaps between about 11 and about 14 cm.

Depending upon the materials of construction chosen and their variousthicknesses, pre-inflation collapsed implant volumes may be in the rangeof 0.02 cm³ to about 5.0 cm³ and perhaps in the range of about 1.0 cm³to about 2.0 cm³. These dimensions allow the implant, when properlycollapsed, to be swallowed by a patient.

FIG. 28 provides a perspective view of the variation of our implant(320) shown in FIG. 27A, differing in that the device is in a collapsedform and has not yet self-inflated. Again, the depicted implant will yetbe collapsed further so to be swallowable. Also visible in FIG. 28 is anoptional fold line (322) and a component (324) of the gas generatingcomposition discussed above. The fold line (322) may be used, ifdesired, to provide an added restriction preventing contact between thecomponents of the gas generator prior to the implant's (320) unfoldingin the stomach. The use of the fold line in this and certain othervariations will be explained in more detail below.

FIG. 29 shows a top view of the expanded implant (320) otherwise shownin FIGS. 27A and 28. Fold line (322) and a component (324) of the gasgenerating composition as discussed above are also shown.

FIG. 30 shows a partial sectional view of a stomach (340) with ourself-deployed implant (342) in place against the stomach wall (344)showing the folds of the mucous membrane. Additional anatomical featuresof the stomach shown are the entry to the stomach (340), the esophagus(346), and the exit of the stomach (340), the pylorus (348). The pylorus(348) leads to the duodenum (350). The various layers of stomach muscle(352, 354, 356) are also shown.

The nerves in the stomach (340) are the terminal branches of the rightvagus nerve (358) and the left vagus nerve (360). The right vagus nerve(358) is distributed on the back of the stomach and consequently thosedistributed nerve branches are not seen in FIG. 30. The left vagus nerve(360) branches on the front of the stomach (340) and those branches aredepicted in FIG. 30 on the front surface of the stomach (340). A greatnumber of branches from the celiac plexus branch of the sympatheticnerve are also distributed to the stomach. Nerve plexuses are found inthe submucous coat in the stomach wall (344) and between the variousmuscle layers (352, 354, 356). From these plexuses, nerve fibrils aredistributed to the muscular tissue (352, 354, 356) and the mucousmembrane (344). The interior lateral diameter “ILD” (362) of the stomach(340) is also seen.

It is the pressure on these highly branched nerves that the implant(342) is to provide in operating to provide a feeling of satiation.

FIG. 31 shows a perspective view of another variation of ourself-expanding implant (370) in its expanded form. The toroidal outershape (372) is given accentuated diametric stiffness by the three radialribs (374).

FIG. 32 shows a perspective view of another variation of theself-expanding implant (376) having a flat ring or toroidal region(378), the periphery (380) of which is configured to contact the stomachwall. A half-loop (382) helps to maintain the regularity of the toroidalregion (378) and is available to provide pressure against the stomachwall if the alignment of the toroidal region (378) of the implant (376)is not directly across the stomach.

FIGS. 33A-33E show a number of expandable envelope shapes that may beinflated with a modest amount of gas and by extension, using smallamounts of reactants. One significant advantage of the toroidal ordonut-shaped inflatable envelope discussed above is that the package tobe swallowed may be made quite small and yet the exterior dimensions arecomparatively extensive. That shape is able to provide a stablestructure able to provide significant and widespread pressure on thestomach wall for producing the “fullness” sensation. The shapes found inFIGS. 31 and 32 and in FIGS. 33A-33E also provide such advantages.

FIG. 33A shows a perspective view of an expanded implant (384) that hassemi-circular ends (385) separated by two relatively straight sections(386). The rounded ends (385) provide surfaces that are broad and coverlarge sections of the stomach wall allowing good predictability thatsome portion of the stomach nervous system will be under pressure. Thestraight sections (386) are, in effect, structural beams that press theends (385) against the stomach wall.

FIG. 33B shows a perspective view of an expanded implant (387) havingthe shape of a multiple-armed cross. The cross arms extends to pressvarious generally opposing areas of the stomach wall. It is a sturdystructure.

FIG. 33C-1 shows a perspective view of an expanded implant (387) havingthe shape of skeletal 3-pyramid. FIG. 33C-2 shows a cross-section of theFIG. 33C-1 implant. This shape is a determinate form and has roundedcorners (390) for contacting the stomach wall. Because thetriangle-based pyramid shape includes a determinate structure, the shapeprovides a variety of sites for pressing into the stomach wall.

FIG. 33D shows a perspective view of an expanded implant (392) havingthe shape of a bi-folded disc.

FIG. 33E shows a perspective view of an expanded implant (394) havingthe shape of a Moebius strip. The twist (396) in the form provides ameasure of stiffness to the overall structure.

FIG. 34A provides a partial cutaway view of a hoop- or ring-shapedvariation (400) of our expandable implant and further shows analternative placement of the gas generator (402) within the hoop. Thisgas generator configuration is shown in FIG. 34A is further shown in thecutaway of FIG. 34B. The container or canister (402) includes twovolumes (406, 408), each of the volumes containing one of the reactants,e.g., base or acid. The two reactant-containing volumes (406, 408) areseparated by the wall (410). Each of the opposing, rounded walls (412,414) includes a number of openings (416) that either allows a liquidreactant in or out. In any case, a liquid reactant present in volume(408) leaves that volume through the openings and must travel completelyaround the interior of torus (403 in FIG. 34A) to approach the otherside of container (402) and to pass through the openings in the oppositevolume (406) and initiate the reaction to produce the inflating gas.This arrangement permits ease of gas producer canister (404)installation and yet separates the reactants by a maximum path.

FIG. 35 shows a side cross-section of a self-expanding implant in threestages to demonstrate a variation for placing the two components of thegas-producing composition in isolation until appropriate for reactionand resultant gas production. Shown as the starting construction of theFIG. 35 procedure is an uninflated implant (440) having a centralopening (442) with an upper flat surface (444) and a lower flat surface(446). A first component (448) is located in a first volume (450) and asecond component (454) is located in the remote second volume (456).

In “Step 1,” the uninflated implant (440) with the included firstcomponent (448) and the second component (454) is then rolled tightlywhile maintaining the isolation of the two components. The rolledimplant (440) is then coated with a biodegradable material, e.g., agelatin layer (458) to form a coated swallowable implant (460). Althoughthe liquid may be expected to exhibit some tendency to migrate betweenthe layers forming the upper (444) and lower surfaces through capillaryaction to the reactive other component, it is our experience that suchoccurrence is rare. The tighter the roll, the less tendency has theliquid to migrate. Although not wishing to be bound by this theory, weconjecture that any reaction that takes place through liquid seepageraises the system pressure within the rolled device and pushes theliquid back into its volume.

In “Step 2,” the coated implant (460) is swallowed and the bioerodiblecovering (458) is dispersed allowing the tightly rolled implant tounroll and to allow the first component found in the first volume tomove to and to react with the second component found in second volume(456) to form a gas, inflating the device and form an inflated implant(462).

FIG. 36 shows another schematic device for self-inflating the implant.As is the case above, at least one of the components is liquid. In thisvariation, a first, liquid component (460) is located in a first volume(462) potentially having a closable opening or openings only into asecond volume (466) containing and a second liquid or solid component(464). The second volume (466) includes a passageway (468) into theinflatable bladder or envelope forming the implant. The first component(460) and the second component (464) together comprise the gas-producingcomposition.

The passageway (472) between the first volume (462) and the secondvolume (466) is temporarily closed using a plug (474) that is held in aclosed position using a thread (476). Spring (478) pushes upon plug(474) and thereby biases the plug (474) to open. Thread (476) pullsagainst the spring. If thread were not there, as is the case in thelower panel of FIG. 36, the spring (478) compression would open the plug(474).

Exterior to the implant is a digestible knot (480) or the like that,once digested or eroded in the stomach as shown in the lower panel ofFIG. 36, allows the thread (478) to slip through the upper wall and, inturn, allows the spring (474) to push the plug (474) into the firstvolume (462) and displace some of the first liquid component (460) intothe second component (464) in second volume (466) producing inflatinggas that escapes through opening (468) to inflate the implant (470). Thespring (474) may be formed of a biodegradable polymer such aspolyglycolic acid.

FIG. 37 shows a generally similar arrangement to that of FIG. 36, butwith a different sealing or valving arrangement. In this variation, thepassageway (472) between the first volume (462) and the second volume(466) is temporarily closed using a flexible, polymeric, magneticflapper (490) optionally having a magnetic seat (492) surroundingopening (472).

The flapper (490) may comprise a polymeric, flexible material including,for instance, ferromagnetic particles. The ferromagnetic particleloading should be sufficient to allow a magnet (500) move the flapper(490) away from opening (472) as shown in the lower panel of FIG. 37 andto allow fluid (460) from first volume (462) into second volume (466)for reaction to gas ultimately flowing through opening (468) to inflatethe implant. In practical operation, a magnet could be applied to apatient's stomach area to open flapper (490) and initiate gasproduction.

FIG. 38 shows still a similar arrangement to that shown in FIG. 37 butinstead utilizing a thermoplastic sealant (502) to hold flapper (504) inplace against a spring (506) in compression until released byapplication of radiofrequency energy (508) to melt the thermoplasticsealant (502) and to allow fluid (460) from first volume (462) intosecond volume (466) for reaction to gas ultimately flowing throughopening (468) to inflate the implant. Desirably such a thermoplasticsealant (502) would have a fairly low softening point and be loaded witha material such as ferromagnetic or ferrimagnetic particles that tend toconcentrate the RF energy into the sealant for softening.

FIG. 39 simply shows a volume (510) that contains one of the components(512) of the gas-producing composition and the presence of a fold line(514) to concentrate sealing forces at that line (514) when folded (asshown in the lower panel of FIG. 39) and to maintain the isolation ofthe component (512) within volume (510).

The folded construct may simply be folded, as is, into a roll such asfound in Step 2 of FIG. 35 to help maintain isolation of reactants untilneeded for gas expansion.

Another set of structures suitable for maintaining separation betweenthe components of the gas-producing composition are those wecharacterize as “frangible” structures. By “frangible” structures, wemean those structures that maintain separation between the twocomponents until some exterior movement or pressure causes a physicalfracture of at least some portion of the structure permitting contactbetween and consequent chemical reaction between the components of thegas-producing composition. As is the case with each of the gas-producingcompositions discussed above, either or both of the components may be ina liquid, solid, semisolid, or gel form.

The impetus for physically fracturing some portion of the frangiblestructure may be any intracorporal movement or pressure, natural orapplied. Pressures such as those caused as a result of peristalticmotion or the act of swallowing or physical pressure applied fromoutside the body (e.g., due to a health professional pressing on thestomach) may be used to fracture the fracturable component of thefrangible structure. Movements such as that involved with unfolding theballoon after dissolution of the outer capsule, peristaltic motion, orphysical manipulation of the frangible structure may be used to fracturethe fracturable component of the frangible structure.

The region of fracture may be widespread, e.g., destruction of astructural wall in the frangible structure, or narrow, e.g., the openingof a small passageway or hole allowing contact between the gas-producingchemicals. The relative size of the region of fracture may be betweenthese extremes.

A wide variety of materials are suitable for use in the fracturablecomponent of the frangible structure. Waxes such as petroleum waxes,bees wax, polyethylene waxes, are suitable. Natural materials (or thosederived from natural materials) such as hard gelatins, rice and wheatnoodle materials, starch-based compositions perhaps comprisingpotato-starch with or without synthetic and natural polymers, may beused as some portion of the fracturable components. The fracturablecomponent may comprise regions of non-fracturable materials (perhapsdissolvable in stomach fluids such as polyglycolic acid membranes) edgedby fracturable materials.

FIGS. 40A-40C show side-view cross-sections of three frangiblestructures having outer fracturable coverings. FIG. 40A shows agenerally square-cornered structure (600) having an outer fracturablecover (602) and containing one or the other of the gas-producingchemicals. FIG. 40B shows a structure (606) having a parallelogramcross-section that, because of its non-right-angle corners, willfracture under pressure more easily than will the structure shown inFIG. 40A. FIG. 40C shows a structure (610) with regions (612) thatprovide ease of stress-fracture. The hillocks (612) need not have thespecific shape shown there to achieve enhanced fracturably. Other shapeshave stress-concentrating abilities.

FIGS. 41A-41C show structures in which one or more fracturable surfacesare used to maintain a separation between the gas-producing components.FIG. 41A shows a frangible structure (614) having two fracturablesurfaces or walls (616) and a central wall (618), all combining toenclose a first gas-producing solid or fluid (620) and a secondgas-producing solid or fluid (622). The central wall (618) may befracturable or not. FIG. 41B shows a frangible structure (624) in whicha fracturable central wall (626) is used to separate a firstgas-producing solid or fluid (620) and a second gas-producing solid orfluid (622). FIG. 41C shows a frangible structure (627) having an outersurface or wall (628) and central wall (630) used to separate a firstgas-producing solid or fluid (620) and a second gas-producing solid orfluid (622).

The structures shown in FIGS. 40A-40C and 41A-41C might be introducedinto the expandable bladder, balloon, or envelope but not necessarilyaffixed to the interior of the envelope or balloon.

FIG. 42 shows a frangible structure (640) in which a fracturable wall(642) contains one of the first or second gas-producing solid or fluid(644) in conjunction with a portion of the expandable envelope (646).Two (or more) of these fracturable walls may be used in a singleexpandable envelope to enclose selected amounts of the first or secondgas-producing solid or fluids. The multiple structures need not be allof the same size.

FIG. 43 shows before-and-after, cross-section, side-views of a frangiblestructure (650) having at least one interior fracturable wall (652). Theoverall structure of the device (650) includes three containment volumesor regions (654, 656, 658). The small volume (654) is isolated from theadjacent chamber (656) by fracturable wall (654) and contains either ofan acid or a base. The adjacent or middle chamber (656) contains acid(if the small chamber (654) contains base) or a base (if the smallchamber (654) contains an acid). The final chamber (658) contains anacid or base as is found in the small chamber (654).

This structure helps to enhance the mixing of the reactants. When thefracturable wall (652) breaks, as shown in part (b) of FIG. 43, thesmall amount of reactant in volume (654) reacts with the complementaryreactant in chamber (656) to form a gas and that expansion pushes thereactant in middle chamber (656) through a thin wall (660) betweenchamber (656) and chamber (658)) and into the end chamber (658) to causereaction of the reactant in chamber (656) and that in chamber (658) andto form the larger bulk of gas. The expansion of the gas will forcethrough thinned end wall (662) into the outer envelope for expansion ofthat envelope.

One or more of thin walls (660, 662) may be fracturable regions, if sodesired.

FIG. 44 shows before-and-after, cross-section, side-views of a frangiblestructure (670) having at least one interior fracturable joint (672)separating two volumes (674, 676) containing the two gas-producingchemicals. Bending the fracturable joint (672), as seen in portion (b)of FIG. 44, both opens the passageways to the two volumes (674, 676) andopens the joint to the interior of the expandable envelope. FIG. 45shows a close-up side view of the fracturable joint (672) found in thedevice of FIG. 44. These types of frangible seals have been usedextensively. See, for instance, U.S. Pat. No. 4,790,429, to Fukushima.

Finally, FIG. 46 shows a frangible structure (680) in which a pair ofwalls (682, 684), adherent to the envelope wall (686), each define avolume (688, 690) containing one of the first or second gas-producingsolid or fluid (692, 694). The walls are joined at a fracturable joint(696) of the type described in conjunction with FIGS. 44 and 45.Fracture of the fracturable joint (696) allows contact of the reactantgas-producing chemicals and expansion of the envelope.

Methods of Use

The described implant is used in the following fashion: the swallowabledevice is (a) administered orally to the patient in a collapsedconfiguration, (b) transported to the stomach, (c) expanded in thestomach to an approximate predetermined size providing pressure on thestomach wall, perhaps by expansion of an expandable member or uponerosion of a shape stabilizer, (d) disassembled after a predeterminedperiod of time by bioerosion and (e) evacuated from the stomach.

The described devices may be used to curb appetite. This treatmentcomprises the step of periodic oral administration of biodegradableself-inflating intragastric implant constructed from one or morediscrete expandable members. The intervals between each administrationare determined by a medical professional after taking into account thephysiological and mental characteristics of the patient. This treatmentis especially useful wherein the deflated implant is swallowed beforemeals such that the food intake during the meal and afterwards isdecreased.

Biodegradable Polymers

Bioerodible or biodegradable polymers include, without limitation,biocompatible polymers that are may be bioerodible by cellular action orare biodegradable by action of body fluid components, such as thosefound in gastric juices. Such polymeric substances include polyesters,polyamides, polypeptides, polysaccharides, and the like. Suitablebiocompatible, biodegradable polymers, include polylactides,polyglycolides, polycaprolactones, polyanhydrides, polyamides,polyurethanes, polyesteramides, polyorthoesters, polydioxanones,polyacetals, polyketals, polycarbonates, polyorthocarbonates,polyphosphazenes, polyhydroxybutyrates, polyhydroxyvalerates,polyalkylene oxalates, polyalkylene succinates, polymalic acid,poly(amino acids), polymethyl vinyl ether, polymaleic anhydride, chitin,chitosan, and their block and intimate copolymers, terpolymers, orhigher polymer-monomer polymers and combinations and mixtures thereof.Many of the more operable biodegradable polymers are degraded byhydrolysis.

These polymers may be either surface erodible polymers such aspolyanhydrides or bulk erodible polymers such as polyorthoesters.Poly(1-lactic acid) (P1LA), poly(dl-lactic acid) (PLA), poly(glycolicacid) (PGA), polycaprolactones, copolymers, terpolymer, higherpoly-monomer polymers thereof, or combinations or mixtures thereof arevery useful biocompatible, biodegradable polymers. One very usefulbiodegradable copolymer comprises a lactic acid and glycolic acidcopolymers sometimes referred to as poly(dl-lactic-co-glycolic acid)(PLG). The co-monomer (lactide:glycolide) ratios of thepoly(DL-lactic-co-glycolic acid) commercial materials are typicallybetween about 100:0 to about 50:50 lactic acid to glycolic acid.Co-monomer ratios between about 85:15 and about 50:50 lactic acid toglycolic acid are quite suitable. Blends of PLA with PLG, e.g., betweenabout 85:15 and about 50:50 PLG to PLA, are also used to preparesuitable polymer materials.

PLA, P1LA, PGA, PLG, their combinations, mixtures, alloys, and blendsare among the synthetic polymers approved for human clinical use. Theyare used as surgical suture materials and in various controlled releasedevices. They are biocompatible and their degradation products compriselow molecular weight compounds, such as lactic acid and glycolic acid,which enter into normal metabolic pathways. Furthermore, copolymers ofpoly(lactic-co-glycolic acid) offer the advantage of a large spectrum ofdegradation rates, the time-to-failure of a selected filament rangingfrom a few days to years by simply varying the copolymer ratio of lacticacid to glycolic acid.

To enhance bio-degradation of the biodegradable polymers listed above,those polymeric compositions may also include enzymes chosen tofacilitate the biodegradation of those polymers. Suitable enzymes andsimilar reagents are proteases or hydrolases with ester-hydrolyzingcapabilities. Such enzymes include proteinase K, bromelaine, pronase E,cellulase, dextranase, elastase, plasmin streptokinase, trypsin,chymotrypsin, papain, chymopapain, collagenase, subtilisn,chlostridopeptidase A, ficin, carboxypeptidase A, pectinase,pectinesterase, various oxidoreductases, various oxidases, and the like.The inclusion of an appropriate amount of such a degradation enhancingagent may be used to regulate implant erosion time.

Enteric Coating Materials

Enteric coating materials suitable for use in our device may be selectedfrom known aqueous enteric film coating systems, such as aqueousdispersions of acrylic resins, especially, polymethacryl methacrylatecopolymers, and dispersions of acetates, especially, cellulose acetatephthalate polymers. Suitable members include acrylic-based resins,azopolymers, polymers of polyvinylacetate and polyacrylic acid,copolymers of methacrylic acid and methylmethacrylate, methylcellulose,carboxymethylcellulose, hydroxypropylcellulose, andhydroxypropylmethylcellulose, polyvinyl acetyldiethylaminoacetate,cellulose acetatephthalate and ethyl cellulose, and copolymers ofmethacrylic acid and methyl methacrylate. Adjuvants such as shellac,talc, stearic acid, and a plasticizer may also be included. Suitablecompositions may be obtained by esterifying a carboxyalkyl group ofcarboxyalkyl cellulose, such group selected fromhydroxypropylmethylcellulose (HPMC), hydroxypropylcellulose (HPC),carboxymethylcellulose, and sodium or calcium salts thereof; carraginan,anginic acid, and magnesium, sodium, and calcium salts thereof;povidone, polyvinylalcohol, tragacanth gum, chitosan, and chitin;elastic polymers, rubbers, bio-rubbers, or silicones; poly(glycerolsebacate) and/or its derivatives; fluoropolymers such aspolytetrafluoroethylene (PTFE), ePTFE, and fluorinatedethylene-propylene resins (FEP); polyethylene terephthalate (PET);Hytrel polyesters; various aromatic polymers, and certain forms ofpolyethereketone (PEEK); various of the Nylons, especially Nylon 12;biodegradable and bioabsorbable elastomers such as hydrogels,elastin-like peptides, poly hydroxyalkanoates (PHA's), and biodegradablepolymers such as poly(lactide), poly (glycolide), and their copolymers(PLGA); alginate and sodium alginate, polyethylene glycol and itsderivatives.

Other suitable materials include hydrogels, acetal copolymers andhomopolymers. Acrylonitrile butadiene styrene (ABS) and mixtures of ABSwith polycarbonates, polyamides, polyimides, polyacrylates, polyarylsulfone, polycarbonates, polyetherimide, polyether sulfone,polyphenylene oxide, polyphenylene sulfide, polypropylene, polysulfone,polyurethane, polyvinyl chloride, and styrene acrylonitrile aresuitable. Various materials such as animal-originated intestine, bowelsor the like, starch, pasta, pre-gelatinized starch, lactose, mannitol,sorbitol, sucrose, and dextrin are suitable. Other approved materialssuch as Carbomer 910, 934, 934P, 940, 941, or 1342, calcium carbonate,calcium phosphate dibasic or tribasic, calcium sulfate, and talc.Amine-based polymers such as poly(allylamine hydrochloride) crosslinkedwith epichorohydrin arid alkylated with 1-bromodecane and(6-bromohexyl)-trimethylammonium bromide; polymers that are made bypolymerizing an aliphatic amine monomer, e.g., a saturated orunsaturated, straight-chained, branched or cyclic non-aromatichydrocarbon having an amino substituent and optionally one or moreadditional substituents.

Metallic Bioerodible Materials

Metallic bioerodible materials include the metals magnesium, titanium,zirconium, niobium, tantalum, and zinc. Silicon is a bioerodiblesemi-metal. Mixtures and alloys of these materials are also bioerodible,e.g., certain zinc-titanium alloys, for example, as discussed in U.S.Pat. No. 6,287,332, to Bolz et al.

The physical properties of such alloys may be controlled both byselection of the metal and by selecting the relative amounts of theresulting alloy. For example, addition of about 0.1% to 1% weight oftitanium reduces the brittleness of crystalline zinc. The addition ofgold to the zinc-titanium alloy at a weight percentage by weight of 0.1%to 2% reduces the alloy's grain size and raises the tensile strength ofthe material.

Other bioerodible metallic alloys include the materials discussed justabove and one or more metals selected from lithium, sodium, potassium,calcium, iron, and manganese. The materials from the first group mayform an oxidic coating that is somewhat resistive to erosion uponexposure to gastric fluids. The metals from the second group arecomparatively more erodible in gastric fluids and promote thedissolution of the otherwise resistive coating.

Further details relating to the latter alloys are also found in U.S.Pat. No. 6,287,332 to Bolz et al., which is incorporated herein byreference in its entirety.

Magnesium alloys are particularly suitable members of this class. Thealloys, for instance, may comprise an alloy of lithium and magnesiumwith a magnesium-lithium ratio of about 60:40, optionally containingfatigue-improving components such as zinc. Sodium-magnesium alloys arealso suitable.

Adjuvant Compositions

The body of the implant may also comprise adjuvant compositions such asmay be selected from therapeutic compositions, slow-release therapeuticcompositions, medications, pH buffers, anti-acid compositions,anti-inflammatory agents, antihistamines, additives, lubricants, uvcontrasting agents, ultrasound contrast agents, radio-opacifiers,diagnostic agents, digestive-related therapeutic agents, probioticbacteria cultures or any combination thereof. Depending upon theadjuvant composition and the material in the implant body, the adjuvantmay be infused into, mixed with, or coated onto the implant body.

We claim:
 1. A method for curbing appetite in a patient comprising steps of: a. introducing a compacted, swallowable, self-expanding, temporary gastric implant into a stomach of the patient; and b. inflating the gastric implant, when in the stomach, to a predetermined size and shape; thereby creating a feeling of fullness and curbing the appetite; wherein the inflating of step (b) is affected by the presence of the implant in the stomach of the patient, wherein the gastric implant is selected from the group consisting of: a. a gastric implant comprising: i. at least one expandable envelope having an interior and an exterior, the envelope configured to seal temporarily, after the implant has been swallowed by the patient, the interior of the envelope from gastric fluid in the stomach at least until an integral, frangible gas-producing composition in fluid communication with the interior of the envelope produces a gas to expand the envelope to a pre-selected size, the envelope, when expanded, contacts walls of the stomach sufficiently to produce a sensation of fullness in the stomach; and wherein the envelope is operable to maintain expansion for the pre-selected period of time and, ii. an integral, frangible gas-producing composition configured to produce a gas after being swallowed by the patient and upon fracture of at least a portion of the integral, frangible gas-producing composition; and, b. a gastric implant comprising: i. at least one expandable envelope including at least one bioerodible material, the envelope having an interior and an exterior, a toric shape upon expansion, and a pre-selected diameter that, upon expansion, contacts walls of the stomach sufficiently to produce a sensation of fullness in the stomach, the envelope operable to maintain expansion for a pre-selected period of time; ii. a gas-producing composition operable to produce carbon dioxide gas for expansion of the at least one expandable envelope after being swallowed by the patient, the expansion affected by the presence of the implant in the stomach, and, iii. an enclosure including a bioerodible material, the enclosure enclosing the expandable envelope and gas-producing composition prior to expansion, and having a size suitable for swallowing by the patient; and wherein the gastric implant comprises: a. a plurality of discrete expandable elements; and, b. attaching means adapted to attach each of the discrete expandable elements to at least one other discrete expandable element.
 2. The method according to claim 1, wherein the introducing of step (a) further comprises swallowing of the gastric implant by the patient.
 3. The method according to claim 1, wherein the introducing of step (a) further comprises endoscopically implanting the gastric implant into the stomach of the patient.
 4. The method according to claim 1, wherein the inflating of step (b) further comprises contacting at least part of the gastric implant with at least part of an interior wall of the stomach, wherein the contacting creates a feeling of fullness, thereby curbing the appetite of the patient.
 5. The method according to claim 1, wherein the gas produced is carbon dioxide.
 6. The method according to claim 1, wherein the gas-producing composition comprises a base and an acid.
 7. The method according to claim 6, wherein (a) the base is selected from the group consisting of sodium bicarbonate (NaHCO₃), sodium carbonate (Na₂CO₃), calcium bicarbonate (Ca(HCO₃)₂), calcium carbonate (CaCO₃), and mixtures thereof, and (b) the acid is selected from the group consisting of vinegar, acetic acid, citrus juices selected from the group consisting of lime, lemon, orange, and grapefruit juices and their mixtures, ascorbic acid, tartaric acid, and mixtures thereof.
 8. The method according to claim 1, wherein the integral, frangible gas-producing composition comprises a base and an acid, and further comprises at least one fracturable region that at least partially contains at least one of the base and the acid, the fracturable region configured to allow contact of the base and the acid upon fracture of the fracturable region after the swallowing by the patient.
 9. The method according to claim 8, wherein the at least one fracturable region comprises at least one fracturable wall that at least partially contains at least one of the base and the acid.
 10. The method according to claim 9, wherein the at least one fracturable wall wholly contains one of the base and the acid.
 11. The method according to claim 9, comprising more than one fracturable wall containing the base and the acid.
 12. The method according to claim 9, wherein the at least one fracturable wall and the expandable envelope in combination comprise at least one of the base and the acid.
 13. The method according to claim 9, wherein the at least one fracturable wall comprises more than one fracturable wall that in combination with the expandable envelope contain the base and the acid.
 14. The method according to claim 8, wherein the at least one fracturable region comprises at least one fracturable joint, the fracturable joint allowing contact of the base and the acid upon fracture of the at least one fracturable joint after the swallowing by the patient.
 15. The method according to claim 8, wherein the at least one of the base and the acid is partially contained by the expandable envelope.
 16. The method according to claim 1, wherein the inflating of step (b) further includes inflating the gastric implant to a shape that allows continued passage of material through the stomach while the implant is inflated.
 17. The method according to claim 1, wherein the inflating of step (b) further includes inflating the gastric implant to a shape selected from the group consisting of toric, X-shaped, Plus-shaped, ovoid, truncated ovoid, half-football shaped, toroid, bridged toroid, ring-shaped, spiral, Moebius strip, cylindrical, conical, truncated conical, cup-shaped, multiple-armed cross, skeletal pyramidal, double flexed washer, and stomach-shaped.
 18. The method according to claim 1, wherein the inflating of step (b) further includes inflating each of the plurality of discrete expandable elements according to a predetermined sequence.
 19. The method according to claim 1, wherein the inflating of step (b) further includes inflating each of the plurality of discrete expandable elements at a predetermined time of between about 0.25 hour and about 30 days from a time that the implant reaches the stomach.
 20. The method according to claim 1, further comprising a step (c) of disassembling the gastric implant.
 21. The method according to claim 1, further comprising a step (c) of disassembling the gastric implant by: i. disassembling each of the discrete expandable elements individually; ii. detaching the discrete expandable elements from the attachment means individually, and iii. evacuating the gastric implant from the stomach of the patient, wherein the evacuating includes evacuating each of the discrete expandable elements individually from the stomach.
 22. The method according to claim 21, further comprising bioeroding and deflating each discrete expandable element prior to evacuation from the stomach.
 23. The method according to claim 1, wherein the attaching means are selected from the group consisting of thread, cord, and wire.
 24. The method according to claim 1, wherein the attaching means are constructed from material selected from the group consisting of (a) elastomeric materials and (b) shape-memory materials.
 25. The method according to claim 1, wherein the attaching means comprise dual, substantially parallel elastic wires.
 26. The method according to claim 25, wherein the dual, substantially parallel elastic wires are separated by separating means selected from the group consisting of pinch-point joints, joints, and flexible ties.
 27. The method according to claim 1, wherein the attaching means comprise at least one bioerodable material.
 28. The method according to claim 27, wherein the at least one bioerodible material is selected from the group consisting of polyesters, polyamides, polypeptides, polysaccharides, polylactides, polyglycolides, polyanhydrides, polyurethanes, polyesteramides, polyorthoesters, polydioxanones, polyacetyls, polyketals, polycarbonates, polyorthocarbonates, polyphosphazenes, polyhydroxybutyrates, polyhydroxyvalerates, polyalkylene oxalates, polyalkylene succinates, polymalic acid, poly(amino acids), polymethyl vinyl ether, polymaleic anhydride, chitin, chitosan, poly(1-lactic acid) (P1LA), poly(dl-lactic acid) (PLA), poly(glycolic acid) (PGA), polycaprolactones and their block and intimate copolymers, terpolymers and higher poly-monomer polymers thereof, polyvinylacetate and polyacrylic acid, methylcellulose, carboxymethylcellulose, hydroxypropylcellulose, and hydroxypropylmethylcellulose, polyvinyl acetyldiethylaminoacetate, cellulose acetatephthalate and ethyl cellulose, and copolymers of methacrylic acid and methyl methacrylate, hydroxypropylmethylcellulose (HPMC), hydroxypropylcellulose (HPC), carboxymethylcellulose, and sodium or calcium salts thereof, hydrogel, shape memory material, super elastic material, and nickel titanium (NiTi), combinations, and mixtures thereof; and wherein the at least one bioerodible material is integrated into a single combination or a mixture of several combinations thereof, and at least one layer is configured in the expandable envelope.
 29. The method according to claim 1, further including layers configured in the expandable envelope to maintain expansion for the pre-selected period of time.
 30. The method according to claim 1, wherein the gastric implant has an envelope including at least one bioerodable material.
 31. The method according to claim 1, wherein the envelope is compacted by a method selected from the group consisting of rolling and folding.
 32. The method according to claim 1, wherein a bioerodable capsule encloses the envelope and gas-producing composition.
 33. The method according to claim 1, wherein the gastric implant includes a coating selected from the group consisting of a bioerodable coating for enclosing the envelope and gas-producing composition, an enteric coating enclosing the envelope and gas-producing composition, and combinations thereof.
 34. The method according to claim 33, wherein the bioerodable coating comprises gelatin.
 35. The method according to claim 1, wherein the gastric implant has a bioerodable shape stabilizer maintaining a compacted shape of the implant.
 36. The method according to claim 1, wherein the inflating of step (b) further includes applying an external stimulus to initiate inflation of the gastric implant; the external stimulus selected from the group consisting of physical manipulation, an external magnetic field, digestive movements, application of radio-frequency energy, and combinations thereof.
 37. The method according to claim 1, wherein the inflating of step (b) further includes externally manipulating the stomach of the patient in order to initiate inflation of the gastric implant.
 38. The method according to claim 1, wherein the inflating of step (b) further includes bringing to a predetermined value a condition selected from the group consisting of temperature, pH, water activity (a_(w)), water availability in the stomach, and availability of digestive enzymes in order to initiate inflation of the gastric implant.
 39. The method according to claim 1, further comprising a step (c) of disassembling the gastric implant after a predetermined period of time; wherein the disassembling includes a step selected from the group consisting of at least partially deflating the gastric implant; at least partially dissolving at least part of a material of the gastric implant; at least partially eroding at least a part of the material of the gastric implant; at least partially disintegrating at least part of the material of the gastric implant into smaller pieces; at least partially digesting the gastric implant, and combinations thereof.
 40. The method according to claim 1, wherein the gastric implant is selected from the group consisting of an implant having grooves on an external surface, the grooves adapted to accelerate rate of disassembling the gastric implant; an implant having protrusions on an external surface, the protrusions adapted to accelerate rate of disassembling the gastric implant; and combinations thereof.
 41. A method of treating obesity comprising steps of: a. curbing the appetite of an obese patient according to the method of claim 1; and, b. repeating step (a) at times determined by a predetermined protocol; wherein an amount of food ingested by the patient while the implant is within the stomach of the patient is less than that ingested prior to commencement of the method.
 42. The method according to claim 41, further comprising leaving the gastric implant within the stomach of the patient for a predetermined period of time.
 43. The method according to claim 1, wherein the gastric implant is adapted to provide a predetermined amount of pressure against a wall of the stomach upon inflation.
 44. The method according to claim 43, wherein the predetermined amount of pressure is a maximum pressure obtainable for a given quantity of gas-producing composition.
 45. The method according to claim 1, wherein the gastric implant includes at least one adjuvant composition selected from the group consisting of therapeutic compositions, slow-release therapeutic compositions, medications, pH buffers, anti-acid compositions, anti-inflammatory agents, antihistamines, additives, lubricants, ultraviolet contrasting agents, ultrasound contrasting agents, radio-opacifiers, diagnostic agents, digestive-related therapeutic agents, probiotic bacteria cultures, and combinations thereof.
 46. The method according to claim 45, wherein the adjuvant composition is selected from the group consisting of an adjuvant composition at least partially infused into the implant, an adjuvant composition mixed with the implant, an adjuvant composition coated onto the implant, and combinations thereof.
 47. The method according to claim 1, wherein creating a feeling of fullness and curbing the appetite of the patient is obtained after inflating the gastric implant and after the patient introduced food into the stomach. 